| Structural highlights
Function
[RCC1_YEAST] Guanine nucleotide exchange factor that promotes the exchange of GSP1/GSP2-bound GDP by GTP and controls RNA metabolism and transport. Involved in yeast pheromone response pathway and in mRNA metabolism. Involved in nuclear pore complex (NPC) assembly and required for mRNA and ribosome nuclear export. Binds chromatin and is involved NPC-mediated transcriptional control.[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14]
Publication Abstract from PubMed
Prp20p is the homolog of mammalian RCC1 (regulator of chromosome condensation 1) in Saccharomyces cerevisiae, which acts as the guanine nucleotide exchange factor (GEF) for Gsp1p (yeast Ran). Prp20p plays multiple roles in mRNA metabolism, nucleocytoplasmic transport and mitosis regulation. Prp20p also functions as a linker between chromatin and nuclear pore complex (NPC) which regulates the NPC-mediated boundary activity (BA). Prp20p contains an N-terminal nuclear localization signal (NLS) and a typical RCC1-like domain (RLD). Here we present the 1.9A crystal structure of the RCC1-like domain of Prp20p, which exhibits a classical seven-bladed beta-propeller. We also proved that the additional beta-wedge in Prp20p is essential for the interaction between Prp20p and Gsp1p. Based on this structure, we built a complex model of Prp20p and Gsp1p which was optimized by molecular dynamics (MD) simulations. Our model reveals that Prp20p and RCC1 share similar Ran GTPase binding mode. In addition, we also studied the histone-binding property of Prp20p in vitro.
The 1.9A crystal structure of Prp20p from Saccharomyces cerevisiae and its binding properties to Gsp1p and histones.,Wu F, Liu Y, Zhu Z, Huang H, Ding B, Wu J, Shi Y J Struct Biol. 2011 Apr;174(1):213-22. Epub 2010 Nov 18. PMID:21093592[15]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
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- ↑ Aebi M, Clark MW, Vijayraghavan U, Abelson J. A yeast mutant, PRP20, altered in mRNA metabolism and maintenance of the nuclear structure, is defective in a gene homologous to the human gene RCC1 which is involved in the control of chromosome condensation. Mol Gen Genet. 1990 Oct;224(1):72-80. PMID:2277633
- ↑ Clark KL, Ohtsubo M, Nishimoto T, Goebl M, Sprague GF Jr. The yeast SRM1 protein and human RCC1 protein share analogous functions. Cell Regul. 1991 Oct;2(10):781-92. PMID:1666302
- ↑ Fleischmann M, Clark MW, Forrester W, Wickens M, Nishimoto T, Aebi M. Analysis of yeast prp20 mutations and functional complementation by the human homologue RCC1, a protein involved in the control of chromosome condensation. Mol Gen Genet. 1991 Jul;227(3):417-23. PMID:1865879
- ↑ Forrester W, Stutz F, Rosbash M, Wickens M. Defects in mRNA 3'-end formation, transcription initiation, and mRNA transport associated with the yeast mutation prp20: possible coupling of mRNA processing and chromatin structure. Genes Dev. 1992 Oct;6(10):1914-26. PMID:1398069
- ↑ Amberg DC, Fleischmann M, Stagljar I, Cole CN, Aebi M. Nuclear PRP20 protein is required for mRNA export. EMBO J. 1993 Jan;12(1):233-41. PMID:7679070
- ↑ Kirkpatrick D, Solomon F. Overexpression of yeast homologs of the mammalian checkpoint gene RCC1 suppresses the class of alpha-tubulin mutations that arrest with excess microtubules. Genetics. 1994 Jun;137(2):381-92. PMID:8070652
- ↑ Hurt E, Hannus S, Schmelzl B, Lau D, Tollervey D, Simos G. A novel in vivo assay reveals inhibition of ribosomal nuclear export in ran-cycle and nucleoporin mutants. J Cell Biol. 1999 Feb 8;144(3):389-401. PMID:9971735
- ↑ Stage-Zimmermann T, Schmidt U, Silver PA. Factors affecting nuclear export of the 60S ribosomal subunit in vivo. Mol Biol Cell. 2000 Nov;11(11):3777-89. PMID:11071906
- ↑ Brodsky AS, Silver PA. Pre-mRNA processing factors are required for nuclear export. RNA. 2000 Dec;6(12):1737-49. PMID:11142374
- ↑ Baker RP, Harreman MT, Eccleston JF, Corbett AH, Stewart M. Interaction between Ran and Mog1 is required for efficient nuclear protein import. J Biol Chem. 2001 Nov 2;276(44):41255-62. Epub 2001 Aug 16. PMID:11509570 doi:10.1074/jbc.M106060200
- ↑ Clement M, Lavallee F, Barbes-Morin G, de Repentigny L, Belhumeur P. Overexpression of Bud5p can suppress mutations in the Gsp1p guanine nucleotide exchange factor Prp20p in Saccharomyces cerevisiae. Mol Genet Genomics. 2001 Sep;266(1):20-7. PMID:11589573
- ↑ Ryan KJ, McCaffery JM, Wente SR. The Ran GTPase cycle is required for yeast nuclear pore complex assembly. J Cell Biol. 2003 Mar 31;160(7):1041-53. Epub 2003 Mar 24. PMID:12654904 doi:10.1083/jcb.200209116
- ↑ Dilworth DJ, Tackett AJ, Rogers RS, Yi EC, Christmas RH, Smith JJ, Siegel AF, Chait BT, Wozniak RW, Aitchison JD. The mobile nucleoporin Nup2p and chromatin-bound Prp20p function in endogenous NPC-mediated transcriptional control. J Cell Biol. 2005 Dec 19;171(6):955-65. PMID:16365162 doi:10.1083/jcb.200509061
- ↑ Wu F, Liu Y, Zhu Z, Huang H, Ding B, Wu J, Shi Y. The 1.9A crystal structure of Prp20p from Saccharomyces cerevisiae and its binding properties to Gsp1p and histones. J Struct Biol. 2011 Apr;174(1):213-22. Epub 2010 Nov 18. PMID:21093592 doi:10.1016/j.jsb.2010.11.016
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